Tobias Freyer

Frontostriatal activation in patients with obsessive–compulsive disorder before and after cognitive behavioral therapy

BACKGROUND Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder (OCD). However, little is known about the impact of CBT on frontostriatal dysfunctioning, known to be the neuronal correlate of OCD. METHOD A probabilistic reversal learning (RL) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Patients were scanned before and after intensive CBT, controls twice at comparable intervals. RESULTS Strategy change within the RL task involved activity in a broad frontal network in patients and controls. No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons. However, a reanalysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects. A group by time effect was found in the caudate nucleus, demonstrating increased activity for patients over the course of time. Patients with greater clinical improvement, reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, showed more stable activation in the pallidum. CONCLUSIONS Although these findings are preliminary and need to be replicated in larger samples, they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD, the caudate nucleus and the pallidum.

Amygdala hyperreactivity in restrictive anorexia nervosa

Functional imaging studies had often investigated heterogeneous samples of anorexia nervosa (AN) patients with varying paradigms and methodologies that had resulted in divergent results. The present study aimed to examine these issues by studying a well-defined sample of restrictive AN patients with a disorder-specific paradigm which had been used previously. Subjects showed increased blood oxygen level dependent responses of the cingulate, frontal, insular and parietal cortices. Group comparisons demonstrated increased activity of the right amygdala in the sample of restrictive AN patients. Our results are in support of other recently published functional imaging studies and point to a pivotal role of the right amygdala in AN. Signals of the midcingulum were reduced in comparison to healthy controls. The constellation of increased activity of the amygdala and decreased activity of the cingulate cortex likely represents parts of a negative feedback loop of emotional processing. Disgust ratings correlated with the amygdala signal negatively, which points to the complex role of this structure within eating disorders.

Test-retest reliability of event-related functional MRI in a probabilistic reversal learning task

Repeated functional magnetic resonance imaging (fMRI) studies aim to detect changes in brain activity over time, e.g. to analyze the cerebral correlates of therapeutic interventions. This approach requires a high test-retest reliability of the measures used to rule out incidental findings. However, reliability studies, especially for cognitive tasks, are still difficult to find in the literature. In this study, 10 healthy adult subjects were scanned in two sessions, 16 weeks apart, while performing a probabilistic reversal learning task known to activate orbitofrontal-striatal circuitry. We quantified the reliability of brain activation by computing intra-class correlation coefficients. Group analysis revealed a high concordance for activation patterns in both measurements. Intra-class correlation coefficients (ICCs) were high for brain activation in the associated regions (dorsolateral prefrontal, anterior prefrontal/insular and cingulate cortices), often exceeding 0.8. We conclude that the probabilistic reversal learning task has a high test-retest reliability, making it suitable as a tool for evaluating the dynamics of deterioration in orbitofrontal-striatal circuitry, e.g. to illustrate the course of a psychiatric disorder.

Frontocingular Dysfunction in Bulimia Nervosa when Confronted with Disease‐specific Stimuli

OBJECTIVE Bulimia nervosa (BN) is characterized by dysregulation of impulse control, in other words, uncontrolled eating. Functional neuroimaging studies have been sparse and have used variable methodologies. METHOD Thirteen medication-free female BN patients and 13 female healthy controls were investigated by functional magnetic resonance imaging using a disease-specific food paradigm. Stimuli were rated after the scanning procedure. RESULTS Bulimia nervosa patients showed increased fear ratings and a trend for increased disgust. Magnetic resonance imaging data of 10 BN patients could be analysed. Three BN patients had to be excluded from the analysis because of minimal blood oxygen level dependent signals. Compared with healthy controls, BN patients showed less activation of the anterior cingulate cortex, which extended into the lateral prefrontal cortex. Furthermore, the right temporal pole showed decreased reactivity. DISCUSSION This study substantiates a key role of lateral prefrontal dysfunction in BN, a brain region involved in impulse control. Furthermore, the anterior cingulate cortex, which plays a key role in emotion processing, is dysfunctional. A major limitation of this study is the small sample size.

The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder

Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

Quality of life changes following inpatient and outpatient treatment in obsessive-compulsive disorder: a study with 12 months follow-up

BackgroundQuality of life (QoL) is increasingly recognized as a critical outcome parameter in mental health studies. The aim of this study was to investigate different domains of the QoL in persons with obsessive-compulsive disorder (OCD) before and after a multimodal, disorder-specific in- and outpatient treatment.MethodsData of 73 persons with OCD treated in an inpatient setting followed by outpatient treatment were analyzed. The World Health Organization Quality of Life abbreviated (a multidimensional measure of the QoL) and the Beck Depression Inventory were administered prior to (baseline) and 12 months after the inpatient treatment (follow-up).ResultsAt baseline, participants reported a significantly diminished psychological, social, physical, and global QoL compared to the German general population. Environmental QoL was not impaired in the present sample. The QoL was significantly improved at follow-up, except for social QoL, but remained below norm values. The QoL improvement was predicted by improvements of depressive symptoms.ConclusionsThe results indicate that persons with OCD suffer from a very low QoL. The QoL was significantly improved after 12 months of intensive state-of-the-art treatment. However, the QoL indices remained considerably lower than population norm values, indicating the need for additional research into novel treatment options for persons with OCD.

Schlaf, Depression und insomnische Beschwerden

Sleep, Depression and Insomniac Complaints It has been known for long that depressive disorders are almost always accompanied by disturbances of sleep. Neurobiologically oriented sleep research was able to demonstrate that besides unspecific changes of sleep continuity (prolonged sleep onset latency, increased number of waking periods and early morning awakening) there are also specific changes of sleep, like a reduction of slow-wave sleep and a disinhibition of REM sleep in depression. Disinhibition of REM sleep includes phenomena like a shortening of REM latency (i.e. the time between sleep onset and the occurrence of the first REM period) and intensified REM sleep especially at the beginning of the night with an increased REM density (increased frequency of eye movements during REM sleep). These changes have been interpreted within the framework of an animal model of NREM and REM sleep called the reciprocal interaction model. This model postulates that the early occurrence of REM sleep in depression is based on a central nervous imbalance between cholinergic and aminergic neurotransmission. Besides baseline findings of sleep in depression there are other data suggesting a prominent role of sleep and REM sleep regulation for depression. Almost all antidepressants suppress REM sleep, there is a specific therapeutic effect of sleep deprivation in depression and a close link between the occurrence of insomniac symptoms and depression. In this context, it is also worthwhile mentioning that specific cognitive behavioral interventions for insomniac symptoms, such as sleep hygiene, sleep-wake rhythm structuring and cognitive techniques to reduce nocturnal rumination are very effective in the treatment of insomnia. It is also hypothesized that these techniques may serve as a preventive strategy for ensuing depressive disorders.

Nocturnal Serum Leptin Values in Chronic Primary Insomnia: A Preliminary Report. Nchtliche Leptin-Ausschttung bei Primrer Insomnie: eine Pilotstudie

SummaryQuestion of the studyThe reliable evaluation of polysomnographic recordings (PSG) is an essential precondition for good clinical practice in sleep medicine. Although the scoring rules of Rechtschaffen and Kales [86] are internationally well established, they leave some room for different interpretations, and this may contribute to the limited reliability of visual sleep scoring. The German Sleep Society (DGSM) has set up a task force to devise ways to improve scoring reliability in the framework of their quality management programme. The intention was not to revise the rules of Rechtschaffen and Kales (R&K), but to facilitate their reliable application in sleep scoring and to support the development of standardized algorithms for computerized sleep analysis.MethodsThe task force was formed in September 2004 as a subcommittee of the educational panel of the DGSM: The members of the task force are experienced in sleep scoring and have a background either in physiology, neurology, psychiatry, psychology, or biology. The aim of the task force was to provide interpretation aids and, if needed, specifications or amendments to the R&K rules for the scoring of sleep electroencephalogram (EEG) waveforms and patterns. Decisions were based on the nominal group technique of a nominal panel as the formal consensus-building process. The consensus process was based on scoring and face-to-face discussions of at least 40 examples for each pattern in four 2-day meetings.ResultsRelevant EEG patterns for sleep stage scoring are alpha, theta, and delta waves, sleep spindles, K-complexes, vertex sharp waves, and sawtooth waves. If definitions for a given EEG pattern differed in the literature, the nominal group technique resulted in specifications and amended scoring rules for these EEG patterns. A second part including a series of examples with explanatory comments for each of these EEG patterns is under preparation.ConclusionsAmendatory scoring rules of those EEG patterns that are relevant for sleep scoring may contribute to increasing the reliability of visual sleep scoring and to support the development of standardized algorithms for computerized sleep analysis.ZusammenfassungEinleitungDie reliable Evaluation polysomnographischer Ableitungen ist eine wesentliche Voraussetzung für die Gute Klinische Praxis (GCP) in der Schlafmedizin. Obwohl die Auswertungsregeln von Rechtschaffen und Kales (R&K) [86] international gut etabliert sind, lassen diese einigen Interpretationsspielraum. Dies wird als ein möglicher Grund für die relativ eingeschränkte Reliabilität visueller Auswertungen angesehen. Die Deutsche Gesellschaft für Schlafforschung und Schlafmedizin (DGSM) hat daher eine Task Force eingerichtet, die im Rahmen des Qualitätsmanagementprogramms der DGSM Vorschläge zur Verbesserung der Auswertungsreliabilität ausarbeiten soll. Die Intention dieser Task Force ist es nicht, die Regeln von R&K zu revidieren, sondern vielmehr deren reliable Anwendung in der Auswertung von Polysomnographien zu ermöglichen und damit auch die Entwicklung von standardisierten Algorithmen in der computerisierten Schlafanalyse zu unterstützen.ProzedereDie Task Force bildete sich im September 2004 als eine Untergruppe der AG Ausbildung der DGSM. Die Task Force Mitglieder sind erfahren in der Schlafauswertung und sind entweder Physiologen, Neurologen, Psychiater, Psychologen oder Biologen. Das Ziel der Task Force war die Bereitstellung von Interpretationshilfen und—wenn notwendig—von Spezifikationen oder Ergänzungen zu den R&K Regeln zur Erfassung von EEG-Wellenformen und-Mustern. Die Entscheidungen basierten auf einem nominalen Gruppenprozess als formales Konsensusverfahren. Für jedes Element beruhte der Konsens auf der Auswertung mit Gruppendiskussion von mindestens 40 Beispielen pro Wellenform oder EEG-Muster unter Berücksichtigung der Literatur im Rahmen von 4 zweitägigen Treffen.ErgebnisseRelevante EEG-Muster für die Schlafstadienanalyse sind alpha-, theta- und delta-Wellen, Vertexwellen, Schlafspindeln, K-Komplexe und Sägezahnwellen. Sobald die Definitionen für eines dieser Muster in der Literatur divergierten, führte der nominale Gruppenprozess zu Spezifikationen und Ergänzungen der Angaben von R&K. Ein zweiter Publikationsteil in dem die hier erstellten Spezifikationen an einer größeren Anzahl von Beispielen dargestellt werden, ist derzeit in Vorbereitung.DiskussionDie hier vorgestellten spezifizierten und ergänzten Erfassungsregeln für EEG-Muster mit Relevanz für die Schlafstadienanalyse sollen die Reliabilität der visuellen Auswertung verbessern. Gleichzeitig können die Ergebnisse als Grundlage für einen standardisierten Algorithmus der computerisierten Analyse genutzt werden.

Neurobiologische Korrelate bei Essstörungen: eine explorative fMRT-Längsschnittstudie

Einleitung: Erkrankungen aus dem Bereich der Essstorungen betreffen 1–4% der jungen Frauen. Die Verlaufe sind haufig durch Chronizitat und soziale Beeintrachtigung gekennzeichnet. Es wird postuliert, dass Symptome wie Untergewicht und charakteristische Denkmuster, z.B. Angst vor Gewichtszunahme, bei Patienten mit Essstorungen in Zusammenhang mit Veranderungen neuronaler Netzwerke und deren Funktionsweise stehen. Bisherige Untersuchungen mittels fMRT zeigten veranderte Aktivierungsmuster im Frontalhirn (med. prafrontaler Kortex, ant. cingularer Kortex) bei Darbietung von visuellen Nahrungsreizen. Nach unserer Kenntnis findet sich bisher keine Langsschnittuntersuchung bei Essstorungen. Studien zu Angst- und Zwangsstorungen konnten neuronale Veranderungen unter Psychotherapie bzw. im Symptomverlauf zeigen. Das Ziel dieser Pilot-Studie ist es, mogliche Veranderungen der Aktivierungsmuster bei essgestorten Patientinnen nach visueller Stimulation mit Nahrungsreizen im Verlauf zu erheben. Methodik: Es wurden 7 Patientinnen mit Essstorungen und 7 gesunde Kontrollprobandinnen mittels fMRT untersucht. Die 1. Messung der Patientinnen wurde zu Beginn eines intensiven Behandlungsprozesses durchgefuhrt, die 2. Messung folgte nach 3 Monaten. Den Studienteilnehmerinnen wurden 3 Stunden nach der letzten Mahlzeit visuelle Stimuli in Form von Nahrungsmittelaufnahmen auf Tellern und Bilder von Haushaltsgegenstanden auf neutralem Untergrund im Block-Design dargeboten. Symptomveranderungen bei den Patientinnen wahrend der Behandlung wurden uber Veranderungen von Gewicht und Schlankheitsdruck (Anorexie) bzw. Anzahl der Essanfalle und die Skala ‘Bulimie’ des EDI–2 (Bulimie) erfasst. Ergebnisse: Es handelt sich um eine erste explorative Analyse der fMRT-Daten einer Verlaufsuntersuchung bei essgestorten Patientinnen. Eine Untersuchung von Kontrollprobandinnen im Verlauf ermoglicht eine Berucksichtigung von Wiederholungseffekten. Die Abschlussauswertung wird Ende Februar 2007 vorliegen. Literatur: Roffman et al., 2005 Uher et al., 2001 Uher et al., 2004